1. Introduction to Haemostasis
Ahmad Sh. Silmi
Hematologist Msc,FIBMS

2. Course Objectives
Identify the factors that influence the effectiveness of hemostatic processes.
Describe the mechanisms that are involved in the arrest of blood flow from a damaged vessel.
Identify key aspects associated with primary and secondary hemostasis.
Explain the role of various coagulation components in hemostatic processes.
Define the extrinsic, intrinsic, and common pathways that are part of the coagulation cascade, identifying the coagulation factors that are associated with each pathway.
Describe the function of various laboratory tests in evaluating hemostasis.
Identify common coagulation disorders, their symptomology, and subsequent treatment.
Explain the role of the prothrombin time and activated partial thromboplastin time in monitoring anticoagulation therapy.

3. Course outline Part one
An Introduction to the Fundamentals of Coagulation
Introduction to the Fundamentals of Coagulation
Which of the following would NOT impact the effectiveness of hemostatic processes?
Primary Hemostasis
Introduction to Hemostatic Mechanisms
Primary Hemostasis: The Vascular System and Platelet Involvement
Primary Hemostasis: Platelet Production
Primary Hemostasis: Characteristics of the Platelet
Primary Hemostasis: Platelet Function
Summary of Primary Hemostasis
Which of the following processes does NOT occur during primary hemostasis?

4. Course outline Part one Cont.
Overview of Secondary Hemostasis
Secondary Hemostasis: Fibrin Formation via the Coagulation Cascade
Consequences Linked to Deficiencies in Coagulation Factors
What is the ultimate goal of secondary hemostasis?
Coagulation Factors in the Coagulation Cascade
Secondary Hemostasis: The Extrinsic Pathway
Secondary Hemostasis: The Intrinsic Pathway
Secondary Hemostasis: The Common Pathway
Secondary Hemostasis: Coagulation Factor Characteristics
Factor VII is part of which coagulation pathway?
The Fibrinolytic System
Regulation of hemostatic mechanisms

5. Course outline Part Two
Coagulation Disorders
Coagulation Disorders: Inherited
Coagulation Disorders: Acquired
Coagulation Disorders: Platelet Disorders
Coagulation Disorders and Liver Disease
Anticoagulation Therapy
Heparin Therapy
Oral Anticoagulant Therapy
Other

6. Let us Begin……

7. HEMOSTASIS
Haemostasis or Hemostasis (Greek: aimóstasis, from aíma "blood" + stásis "stagnation") is a complex process which continually ensures:
prevention of spontaneous blood loss and
stops hemorrhage caused by damage of vascular system
Most times this includes the changing of blood from a fluid to a solid state and then to fluid state.

8. Function of Haemostasis
Arrests bleeding
Keeps blood in fluid state
Repair and reestablish the blood flow through the injured vessels
Remove haemostatic plug
If any of the above functions is exaggerated or impaired it will cause either thrombosis or hemorrhage respectively; so hemostasis is a balance between thrombosis and hemorrhage

9. Without this balance, the individual may experience either excessive bleeding (poor clot formation or excessive Fibrinolysis)
Vaso-occlusion (uncontrolled formation of thrombin in vascular system, occluding vessels and depriving organs of blood).
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10. Acquired conditions such as DIC, Liver and Kidney diseases.
HEMOSTASIS
There are certain conditions associated with excessive bleeding are referred to as: Hypo-coagulable states.
Such as, Hemophilia or deficiency in one of the plasma coagulation proteins such as factors VIII.
Acquired conditions such as DIC, Liver and Kidney diseases.
In addition to Coagulation promotion, vessel injury initiates Fibrinolysis through endothelial cell release of tissue Plasminogen activators (tPAS).
This is to ensure that excessive coagulation does not occur.
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11. Role of Coagulation in Hemostasis
Coagulation: Is the process where by on vessel injury, Plasma protein, Tissue factors and Calcium interact on the surface of the platelets to form a Fibrin clot.
Platelets provide a surface for the coagulation reaction, and interact with fibrin to form a stable platelet fibrin clot.
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12. HEMOSTASIS
Tissue factors (except Ca and Tissue Thromboplastin) normally circulate in the plasma as inactive proteins.
On activation some factors form enzymatic proteins known as Seiren Proteases that activate other specific factors in the coagulation sequence.
Other conditions are related to uncontrolled thrombosis are called Hyper-coagulable state. This is related to an appropriate formation of thrombi in the vascular vessels that occlude normal blood flow.
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13. Mechanism of Hemostasis
Haemostasis involves a series of delicately balanced physical and biochemical changes following an injury to a blood vessel .
As the most immediate response, the blood vessel constrict
Then platelets adhere and aggregate at the site of the injury and form a plug

14. Mechanism of Hemostasis
These activated platelets secretes substances that initiate the coagulation factors which interact serially, forming a fibrin network or clot in which white cells, red cells and platelets are trapped and form a solid plug of blood ( coagulation) which seals off the injury vessel completely.
Finally slow lysis of the clot, fibrinolysis, begins and the site of the injury is repaired.

15. Components of normal hemostasis
vessels
Tissue
Tissular coagulation factor
Platelets
Thrombocytic
Platelet Coagulation factors
Coagulation (activator & inhibitors)
Humoral
( plasma factors)
Fibrinolysis
(activater & inhibitors)

16. The effectiveness or failure of haemostatic mechanism to control bleeding depends on :
The type & degree of injury.
The size & ability of injured vessel to contract.
The pressure within the vessel & surrounding tissues.
The availability & activity of the platelets.
The quantity & functional ability of blood clotting factors.
The absence of inhibitors.

17. Hemostasis
The hemostatic components remain inert in the presence of intact vascular tissue or endothelium
Following injury, each component must function optimally.

18. Vessel wall, Blood flow & Coagulation Substances
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19. In Case if there is an Endothelial Injury (Bleeding must be prevented at site of injury)
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20. Flow must be Maintained
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21. Virchow Law There are three haemostatic components:
1- The extra-vascular (The tissues surrounding blood vessels) involved in Hemostasis when local vessel is injured.
It plays a part in Hemostasis by providing back-pressure on the injured vessel through swelling and trapping of escaped blood.
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22. HEMOSTASIS
The three haemostatic components
2- The vascular (The blood vessels through which blood flow) it depends on the size, amount, of smooth muscle within their walls and integrity of the endothelial cell lining.
3- The intra-vascular (The platelets and plasma proteins that circulate within the blood vessels).
These components are involved in Coagulation (clot or thrombus formation) or Fibrinolysis (clot or thrombus dissolution).
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24. Phases Three –phase process Primary hemostasis
Coagulation (secondary hemostasis)
Fibrinolysis (Tertiary hemostasis)

25. Phases cont’d I. Primary hemostasis Involves
Blood vessels (vascular vasoconstriction phase and release of tissue or exogenous factors)
Thrombocytes (platelate or endothelial –thrombocyte phase, platelate aggregation and release of platelate factors).
After 3 to 5 minutes , blood flow is arrested with the formation of a platelate plug.

26. provides for definitive hemostasis
Phases cont’d
II. Coagulation
Involves
Plasma coagulation factors (plasma phase)
Platelate factor 3
provides for definitive hemostasis
Takes 5 to 10 minutes by formation of fibrin
Reinforces the platelate plug.

27. Phases cont’d III Fibrinolysis
Essential final step in any hemostasis mechanism,
Enabling in 48 to 72 hours, and a
Return to normal by destroying fibrin and healing the injured vessel.

28. I. Primary hemostasis
Is a result of a three –way interaction between:
Vascular wall
Platelets
plasma coagulation factors
Triggered by
Small injuries to blood vessels
The plasma coagulation factors desquamation (damaging of epithelial cells in pinpricks)

29. Primary hemostasis
Involves:
Vasoconstriction
Platelet adhesion
Platelet aggregation
Platelet secretion

30. Role of Blood Vessels in Hemostasis
Blood flows through the vascular system to and from all parts of the body. The vascular system consists of capillaries, arteries, and veins.
Blood normally carried within vessels whose physical capabilities include Contraction (narrowing) and Dilation, which are controlled by the smooth muscle of the vessel media.
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31. HEMOSTASIS
Vasoconstriction and Vasodilatation provide the means for control blood flow rate and blood pressure.
Substances released from the endothelial cells and sub- endothelial smooth muscles also contribute to normal blood flow and prevent abnormal formation of clot.
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41. Vascular NO functions
NO inhibits platelets' and leucocytes' adhesion to endothelial cells.
It inhibits platelet aggregation
It facilitates the dissolution of small platelet aggregates.
NO affect the fibrinolytic activity by regulating the release of t-PA & PAI-1.
The crucial role of vascular NO in the control of blood fluidity has been demonstrated by the regulation of the bleeding time in humans.

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44. Arachidonic acid Cyclo-oxygenase PLATELET ENDOTHELIAL CELL Thromboxane
Cyclic Endoperoxides
PLATELET
ENDOTHELIAL CELL
Thromboxane
synthetase
Prostacyclin
synthetase
Prostacyclin
(PGI2)
Thromboxane
(TxA2)
Inhibits plt aggregation
Vasodilator
Enhances plt aggregation
Vasoconstrictor

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46. Mediators of Vascular relaxation

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48. Summary of Important Vascular Function
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49. Vascular Endothelium Function
Prostacyclin
Thromboxane A2
ELAMs, ICAMs
von Willebrand factor
Vasodilation, inhibition of platelet aggregation From platelets, constrict muscular arteries Cytokines induce synthesis to promote leukocyte adhesion Promote platelet-collagen adhesion to exposed sub-endothelium

50. Vascular Endothelium Function
Tissue factor pathway
inhibitor
Thrombomodulin
Tissue plasminogen activator
Heparan sulfate proteoglycans
Tissue factor
Anticoagulant- Inhibits coagulation extrinsic pathway
Anticoagulant- Inhibits coagulation by activating protein C system
Anticoagulant- Inhibits coagulation by activating fibrinolysis
Anticoagulant- Inhibits coagulation by activating antithrombin
Procoagulant- Inflammatory cytokines (IL-1, TNF) induce expression

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53. Upon conclusion one can aske the following question